High placental expression of FLT1, LEP, PHYHIP and IL3RA - In persons of African ancestry with severe preeclampsia

Omonigho Aisagbonhi; Tony Bui; Chanond A Nasamran; Hailee St Louis; Donald Pizzo; Morgan Meads; Megan Mulholland; Celestine Magallanes; Leah Lamale-Smith; Louise C Laurent; Robert Morey; Marni B Jacobs; Kathleen M Fisch; Mariko Horii

doi:10.1016/j.placenta.2023.10.008

High placental expression of FLT1, LEP, PHYHIP and IL3RA - In persons of African ancestry with severe preeclampsia

Placenta. 2023 Dec:144:13-22. doi: 10.1016/j.placenta.2023.10.008. Epub 2023 Oct 20.

Authors

Affiliations

¹ Department of Pathology, University of California, San Diego, La Jolla, CA, USA; Center for Perinatal Discovery, University of California, San Diego, La Jolla, CA, USA. Electronic address: oaisagbonhi@health.ucsd.edu.
² Department of Pathology, University of California, San Diego, La Jolla, CA, USA; Center for Perinatal Discovery, University of California, San Diego, La Jolla, CA, USA; Sanford Consortium for Regenerative Medicine, University of California, San Diego, La Jolla, CA, USA.
³ Center for Computational Biology and Bioinformatics, University of California, San Diego, La Jolla, CA, USA.
⁴ Department of Pathology, University of California, San Diego, La Jolla, CA, USA.
⁵ Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Diego, La Jolla, CA, USA.
⁶ Department of Pathology, University of California, San Diego, La Jolla, CA, USA; Sanford Consortium for Regenerative Medicine, University of California, San Diego, La Jolla, CA, USA.
⁷ Center for Perinatal Discovery, University of California, San Diego, La Jolla, CA, USA; Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Diego, La Jolla, CA, USA.
⁸ Center for Perinatal Discovery, University of California, San Diego, La Jolla, CA, USA; Sanford Consortium for Regenerative Medicine, University of California, San Diego, La Jolla, CA, USA; Center for Computational Biology and Bioinformatics, University of California, San Diego, La Jolla, CA, USA; Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Diego, La Jolla, CA, USA.

Abstract

Introduction: Mortality from preeclampsia (PE) and PE-associated morbidities are 3-to 5-fold higher in persons of African ancestry than in those of Asian and European ancestries.

Methods: To elucidate placental contribution to worse PE outcomes in African ancestry pregnancies, we performed bulk RNA sequencing on 50 placentas from persons with severe PE (sPE) of African (n = 9), Asian (n = 18) and European (n = 23) ancestries and 73 normotensive controls of African (n = 10), Asian (n = 15) and European (n = 48) ancestries.

Results: Previously described canonical preeclampsia genes, involved in metabolism and hypoxia/angiogenesis including: LEP, HK2, FSTL3, FLT1, ENG, TMEM45A, ARHGEF4 and HTRA1 were upregulated sPE versus normotensive placentas across ancestries. LTF, NPR3 and PHYHIP were higher in African vs. Asian ancestry sPE placentas. Allograft rejection/adaptive immune response genes were upregulated in placentas from African but not in Asian or European ancestry sPE patients; IL3RA was of particular interest because the patient with the highest placental IL3RA expression, a person of African ancestry with sPE, developed postpartum cardiomyopathy, and was the only patient out of 123, that developed this condition. Interestingly, the sPE patients with the highest IL3RA expression among persons of Asian and European ancestries developed unexplained tachycardia peripartum, necessitating echocardiography in the European ancestry patient. The association between elevated placental IL3RA levels and unexplained tachycardia or peripartum cardiomyopathy was found to be significant in the 50 sPE patients (p = .0005).

Discussion: High placental upregulation of both canonical preeclampsia and allograft rejection/adaptive immune response genes may contribute to worse PE outcomes in African ancestry sPE patients.

Keywords: African; Cardiomyopathy; IL3RA; Immune; Placenta; Preeclampsia.

MeSH terms

Blood Pressure
Cardiomyopathies / complications
Cardiomyopathies / metabolism
Female
Gene Expression Profiling
Humans
Placenta* / metabolism
Pre-Eclampsia* / metabolism
Pregnancy
Rho Guanine Nucleotide Exchange Factors / metabolism
Tachycardia / complications
Tachycardia / metabolism
Vascular Endothelial Growth Factor Receptor-1 / metabolism

Substances

ARHGEF4 protein, human
FLT1 protein, human
Rho Guanine Nucleotide Exchange Factors
Vascular Endothelial Growth Factor Receptor-1
PHYHIPL protein, human
IL3RA protein, human
LEP protein, human

Abstract

MeSH terms

Substances

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